Study of the most frequent genetic alterations and clinical evolution of human cutaneous melanoma patients treated with CSF-470 vaccine or interferon alpha 2b

BIANCHI, AGOSTINA; BRAVO, ALICIA INÉS; TRINCHERO, ALEJANDRA; BARON, ANTONELA; MORDOH, JOSE

Congreso; ? LXII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2017

Human cutaneous melanoma (HCM) is a skin cancer whose incidence and mortality rates have been increasing over the last 30 years. HCM is relatively resistant to both chemotherapy and radiotherapy; however, it is an immunogenic tumor. A therapeutic vaccine anti-HCM, CSF-470, has been developed in our laboratory. CSF-470 has been tested against interferon alpha 2B in phase II clinical study. It has had better results than interferon alpha 2B.HCM is the highest mutated cancer. Recent advances in sequencing techniques have greatly increased the knowledge of key molecular events for its genesis and development. It has become evident that molecular alterations may have different effects on the tumor microenvironment.The aim of this work was to evaluate if there is a relationship between genetic alterations of each patient´s tumor and disease progression; and if a genetic marker may be identified, that correlates with the observed clinical response and may be used to predict whether patients (pts) will respond to CSF-470 vaccine.The most frequently mutated genes and copy number variation in HCM were studied by Nested-PCR and fluorescence in situ hybridization (FISH) respectively, in 12 pts of the phase II CSF-470 clinical trial. It was found that 67% of the tumors harboured BRAF mutations; all of them being V600E. Only one of the tumors had NRASQ61 and NRASG12 mutations, and it also was BRAFWT as expected. PTEN alterations were observed in 3 pts, one of them had a missense mutation and the others had a partial deletion. Point mutations or a small copy number of CDKN2A were observed in 42% of the tumors. 33% of pts had a missense mutation in the DNA-binding domain of P53. No mutations were found in RAC1.No significant correlation could be established between alterations found in the tumors and metastases-free-survival-period of the pts (p>0.05). This suggests that further genomic or transcriptional alterations of tumor cells must be analyzed to predict clinical behavior.